title page
Contents
List of Abbreviations 5
I. Introduction 8
II. Materials and Methods 12
1. Materials and reagents 12
2. Methods 12
2.1. Isolation of the compounds from Forsythiae Fructus 12
2.2. Animals and sensitization 19
2.3. Drug treatment and aerosolized-OVA challenge 19
2.4. Measurement of airway function 20
2.5. Measurement of bronchoalveolar lavage and WBC count in BALF 23
2.6. Histamine assay 23
2.7. PLA₂ assay 24
2.8. EPO assay 24
2.9. Histological staining 25
2.10. Data analysis 25
III. Results 26
1. Identification of chemical structures of compounds 1-3 isolated from Forsythiae Fructus 26
2. Asthmatic responses in lgE-mediated asthma 27
1) Increase in sRaw 27
2) Increase in leukocyte recruitment in BALF 27
3) Increase in inflammatory chemical mediators and enzymes in BALF 27
4) Histopathological changes 28
3. Anti-asthmatic effect of triterpenic acids in the lgE-mediated asthma 29
1) Decrease in sRaw 29
2) Decrease in total leukocytes, neutrophils and eosinophils in BALF 30
3) Decrease in inflammatory chemical mediators and enzymes in BALF 31
4) Improvement of the histopathological changes 32
IV. Discussion 45
V. References 50
VI. 국문초록 61
VII. Abstract 63
감사의 글 65
Table 1. Effects of triterpenic acids on the specific airway resistance (sRaw) after aerosolized-ovalbumin (AOVA) challenge in OVA-sensitized guinea pig 33
Table 2. Effects of triterpenic acids on leukocytes rercuitment in broncholalveolar lavage fluids (BALF) on LAR 37
Table 3. Effects of triterpenic acids on histamine release, EPO and PLA₂ activities in broncholalveolar lavage fluids (BALF). 40
Fig. 1. HPLC analysis of compound 1. 16
Fig. 2. HPLC analysis of compound 2. 17
Fig. 3. HPLC analysis of compound 3. 18
Fig. 4. Diagram of the Double-chambered Plethysmograph (HSE type 855). 22
Fig. 5. Chemical structure of triterpenic acids isolated from Forsythiae Fructus 26
Fig. 6. Time-dependent changes of sRaw in control. 34
Fig. 7. Inhibitory activity of triterpenic acids on sRaw in IAR asthmatic responses. 35
Fig. 8. Inhibitory activity of triterpenic acids on sRaw in LAR asthmatic responses. 36
Fig. 9. Effects of triterpenic acids on total leukocytes in BALF on LAR. 38
Fig. 10. Effects of triterpenic acids on the recruitment of leukocytes in BALF 39
Fig. 11. Effects of triterpenic acids on histamine release in BALF 41
Fig. 12. Effects of triterpenic acids on EPO activity in BALF 42
Fig. 13. Effects of triterpenic acids on PLA₂ activity in BALF 43
Fig. 14. Effects of triterpenic acids on lung in the pathological survey 44